[Calcium influx: an intracellular message of the mitogenic action of insulin-like growth factors].

Insulin-like growth factor-I and II (IGF-I and II) are potent progression factors. In BALB/c 3T3 cells, IGFs exert the progression activity when quiescent cells are pretreated with platelet-derived growth factor and epidermal growth factor. In this IGF-responsive state, which we designated primed competent state, IGF-I and II stimulate calcium influx. The IGF-stimulated calcium influx sustains for at least few hours and is dependent on extracellular calcium concentration. To stimulate calcium influx IGF activates calcium-permeable cation channel. This IGF-sensitive channel is voltage-independent and is not totally selective for calcium. When IGF-mediated calcium influx is inhibited by either reduction of extracellular calcium or by adding cobalt or tetramethrin, IGF-induced DNA synthesis is attenuated. In either case, stimulation of calcium influx rate correlates quite well with the increase in DNA synthesis. Moreover, when calcium influx is augmented pharmacologically in primed competent cells by using BAY K8644, DNA synthesis is increased. These results suggest that calcium influx is an intracellular message of the mitogenic action of IGF-I and II.